Blood Disorders Research Articles

Prevalence of osteoporosis & osteopenia in transfusion-dependent thalassemia in Sulaimaniyah city, Iraq

Background and objectives: Although blood transfusion and iron chelation increase the lifespan of thalassemic patients, these patients face many complications, including osteoporosis and osteopenia. Thus, we aimed to determine prevalence rates of osteoporosis/osteopenia using Dual Energy X-Ray Absorptiometry in transfusion-dependent thalassemia patients and its relationship with chelation agents and body mass index. Methods: This retrospective study included 150 patients with transfusion-dependent thalassemia in the Thalassemia and Congenital Blood Disorders Center, Sulaimaniyah, Iraq, from December 2021 to July 2022. The participant’s information was collected from the hospital database, including sociodemographic characteristics, bone mineral density status, and the number of items used for chelation. A Dual Energy X-Ray Absorptiometry bone scan was used to check the bone mineral density. Results: The mean age of patients was 19.59±7.59, body mass index was 21.23±18.13, and most (53.3%) were females. Dual Energy X-Ray Absorptiometry results showed that 53.3% of the patients had osteopenia, 21.3% had osteoporosis, 36.7% had average bone mineral density, and 6.7% had low bone mineral density for age. In addition, there was a significant difference between the frequencies of bone density disorders in patients who used one chelating agent (46.4%) versus two chelating agents (85%) (P?0.001). Also, there was a significant difference between the incidence of bone density disorders with low and average body mass index (78%) in comparison with overweight and obese patients (8%) (P?0.001). Conclusions: There is a high prevalence of osteoporosis and osteopenia in transfusion-dependent thalassemia patients, which are more prone to trauma and bone fracture.

The relation between serum ferritin level and echocardiographic findings in transfusion dependent thalassemic patients in Slemani City, Kurdistan Region of Iraq.

Background and objectives: Thalassemia patients are at risk of iron overload. Those with transfusion-dependent thalassemia are more likely to experience cardiac problems because repeated blood transfusions cause iron accumulation in the cardiac myocyte. Thus, this study aims to determine the relationship between serum ferritin levels and echocardiographic findings in transfusion-dependent thalassemia patients. Methods: This retrospective analytical cross-sectional study was conducted on 131 patients with transfusion-dependent thalassemia between 1stDecember 2021 to 1stJuly 2022 at the Center for Thalassemia and Congenital Blood Disorder, Slemani, Iraq. The participant’s information, including sociodemographic characteristics such as age, gender, body weight, height, hemoglobin level, serum ferritin, type and duration of chelation therapy, and echocardiographic findings, were collected from the hospital database using a questionnaire. Then, the correlation between serum ferritin levels and echocardiographic results was determined. Results: The mean age of the patients was 21.24 ± 6.28 years, and most of them were males (55.7%), from the urban region (71%) and had an average body weight (68.7%). The mean serum ferritin level was 1876±1743.63 µg/L. The interpretation of the echocardiography results showed 38 patients (29%) had valvular heart diseases. Body mass index has a reverse linear relationship with ejection fraction(P=0.038) and a direct relationship with age(P<0.001). However, no significant association was found between echocardiographic findings and serum ferritin(P=0.83). Conclusions: We found valvular heart diseases among the most common heart disorders in the patients. Suitable interventions and measures can significantly help manage the condition and reduce illness complications.

Interrelation of Blood Microrheological Parameters Measured by Optical Methods and Whole Blood Viscosity in Patients Suffering from Blood Disorders: a Pilot Study

Interrelation of Blood Microrheological Parameters Measured by Optical Methods and Whole Blood Viscosity in Patients Suffering from Blood Disorders: a Pilot Study

Study on the Analysis of Gender Trends Among the First Authors of Publications on Budd-Chiari Syndrome.

Budd-Chiari syndrome (BCS) is primarily a disease of hepatic vein blockage, which involves a backflow of blood to the liver. Although there have been many causes linked to this disease, most commonly, it occurs due to hypercoagulable states and blood disorders. In recent times, there has been a fast spread of knowledge regarding early diagnosis and various treatment modalities, which has enabled the prevention of mortality in most cases. This has primarily spread through research articles published in various journals. Thus, the article aims tocompare the gender trend ratios to identify the associated discrepancies in terms of male and female author contributions who have been the primary authors for articles pertaining to this disease. Methodology:A PubMed database between the years 2013 and 2022 was used for the bibliometric analysis. The gender of the primary author was analyzed by NamSor, an application programming interface (API). The statistical analysis was conducted using R software, the ARIMA model, and graphs were prepared using Datawrapper. Out of 667 articles extracted, the analysis showed that there were 455 (68.2%) first male authors and 212 (31.8%) first female authors. We also formulated various other results, which depicted a higher female-to-male author ratio including various journals and different countries. Although there has been an increasing trend of male authors as compared to female authors, this study found that male authorship for research on this disease is still higher. This study depicts that there is a necessity to draw attention to the inequitable systems favoring men over women for publications. The predictive analysis conducted also helps to foresee the trend in the next few years and explains the necessity of addressing the disparities among both genders in healthcare systems.

Structural screening and molecular simulation identify potential ligands against the K700E hot spot variant and functional pockets of SF3B1 to modulate splicing in myelodysplastic syndrome

Myelodysplastic syndrome (MDS), a blood disorder with ineffective hematopoiesis and risk of transformation to acute myeloid leukemia, is characterized by recurring cytogenetic and molecular alterations. By chromosome analysis, approximately 60% of patients, carry chromosome 5 and 7 alterations, trisomy of chromosome 8 and may also present with increasingly complex karyotypes, especially in higher grade MDS (MDS with refractory anemia and increased blasts type 1 and 2). Moreover, somatic pathogenic variants in genes associated with aberrant mRNA splicing are frequently mutated with SF3B1 the most frequently mutated. In the setting of SF3B1, the K700E hot-spot mutation is present in approximately 50% of cases. Since recent studies have highlighted modulation of functional dynamics in SF3B1 by mutant splicing factors, the objective of the study was to identify potential small molecule modulators against the frequently mutated RNA splicing factor SF3B1(K700E) and functional allosteric sites by using a molecular structure-based approach and a molecular dynamic simulation. To identify potential SF3B1 modulators, we collected a series of chemical compounds from the Zinc and Enamine database. An initial screen followed by further molecular analysis and simulation using the Schrödinger suite was performed. Parameters used to monitor the stability and binding of the protein-ligand complex included: RMSF, protein-ligand contacts, electrostatic, Van Der Waals forces and binding energies (MMGBSA). A 100-nanosecond simulation showed strong binding between selected compounds and key amino acid residues, including the mutation hot-spot K700E and functional allosteric amino acid residue R630. Ligand binding energies between compounds and key amino acid residues ranged from −50.67 to −58.04 kcal/mol. In brief, small molecule modulators show strong binding to SF3B1 suggesting these compounds may be used against cells harboring the K700E variant or to modulate splicing by targeting functional allosteric sites.

MODERN APPROACHES TO THE PHARMACOTHERAPY OF ANEMIA

Anemia is a common blood disorder characterized by a decrease in the number of red blood cells or hemoglobin levels, leading to symptoms such asfatigue, weakness, and shortness of breath. Pharmacotherapy plays a crucial role in managing anemia by addressing underlying causes and restoring normal hemoglobin levels. This article explores the current state of pharmacological treatments for anemia, including erythropoiesis-stimulating agents, iron supplements, and newer innovative therapies such as erythroid maturation agents. It also discusses the challenges and future directions in the field of anemia pharmacotherapy.

Preliminary results of atezolizumab and pirfenidone in non-small cell lung cancer.

e15197 Background: Checkpoint inhibitors (CPI) targeting the PD1/PD-L1 axis improved outcomes for stage IV non-small cell lung cancer (NSCLC). Poor response to PD-L1 antibody has been linked to increased cancer-associated fibroblasts (CAF), which interact with cytotoxic T cells (CTLs) similarly to regulatory T cells (Tregs). CAFs, through cytokine production, impair antitumor immunity by affecting CTL function (TGF beta) and inhibiting CTL recruitment into tumors, suggesting that CAFs could be a therapeutic target in CPI-resistant NSCLC. Pirfenidone (P) exhibits anti-fibrotic effects by blocking fibroblast differentiation into CAFs and suppressing TGF beta production and associated signaling pathways/collagens. Atezolizumab (A) targets PD-L1, inhibiting its interaction with PD-1 and B7-1 (CD80) receptors on T cells. We initiated a phase I/II trial to test the combination of AP in recurrent NSCLC after CPI progression. The phase I study aims to determine the maximum tolerated dose (MTD) of AP and assess its safety and tolerability. The phase II study will evaluate its efficacy. The Exploratory Objectives are to measure circulating levels of TGF beta and investigate the expression of CAF-related proteins. Methods: phase I will enroll 3 patients using P at 801 mg PO TID and A at 1200mg IV every 3 weeks. If there is ≤ 1 Dose Limiting Toxicity (DLT), the study will proceed to phase II. If there are ≥2 DLTs, P will be reduced to 534 mg TID. If there is ≤ 1 DLT at this dose, we will proceed to phase II. If there are ≥2 DLTs, then the study will be terminated. Phase II will enroll 16 patients to assess efficacy. The main inclusion criteria are patients with recurrent NSCLC without actionable mutation, after progression with first-line therapy CPI with or without platinum-based doublet chemotherapy, no more than 2 lines of therapy, measurable disease, ECOG 0-2, and adequate organ function. Results: The study enrolled a total of 5 patients (4 males, 1 female), median age of 63.4; 5 were white; 3 patients did not complete the required 21 days of therapy for evaluation (1 non-compliance, 1 disease progression,1 unrelated Urinary Tract Infection); 2 patients were evaluable for toxicity, without DLT; 1 exhibited a partial response to cutaneous metastatic disease, with overall stable disease, 1 had disease progression. Adverse events (AE) in more than 5% of patients included blood disorders, cardiac, gastrointestinal, administration site, metabolic, musculoskeletal, psychiatric, respiratory, and skin disorders. Serious AEs were noted in 2 patients: one experienced gastrointestinal bowel perforation due to disease progression resulting in death, and the other had a respiratory disorder. Conclusions: The combination of AP did not produce unexpected side effects or reach the dose-limiting toxicity threshold. After the phase I portion is completed, the study will proceed to phase II expansion to enroll patients with recurrent NSCLC. Clinical trial information: NCT04467723 .

The prevalence of sickle cell phenotype and its association with clinical outcomes in patients with solid malignancies.

10563 Background: Sickle cell disease (SCD) is the most common inherited blood disorder in the United States and is caused by a mutation of β-globin ( HBB-Mt). The risk of developing solid malignancies in this population remains controversial, with research showing increased rates of some solid tumors (colon, kidney, and thyroid) and decreased rates of others (breast and male genitourinary). We report the prevalence of HBB mutations across a cohort of solid tumors and clinical outcomes between HBB-Wild type (-Wt) v Mutant (-Mt) tumors. Methods: Non-small cell lung cancer (NSCLC, N = 3307), breast (BC, N = 1960), colorectal (CRC, N = 2161), prostate (N = 899), and gynecologic cancers (N = 2,805) in persons of African descentwere tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing of DNA (whole exome) and RNA (whole transcriptome). Her2/Neu (+: ≥3+ and >10%) and HR (ER or PR+: ≥1+ and ≥1%) expression was tested by immunohistochemistry. Tumors were assessed for single nucleotide variations (SNVs) and insertions/deletions (indels) in HBB associated with a sickle cell phenotype. Mutation prevalence for all other genes was calculated for pathogenic SNVs/indels. Differentially regulated pathways were assessed by gene set enrichment analysis (GSEA). Fisher’s Exact/χ2 tests were applied as appropriate with p-values adjusted for multiple comparisons ( p < .05). Real-world overall survival (OS) and ethnicity data was obtained from insurance claims and log-rank estimates were calculated for molecularly defined subpopulations. Results: Amongst persons of African descent, uterine sarcoma had the highest prevalence of HBB-Mt (17.1%, 43/251) followed by uterine serous carcinoma (9.1, 70/768) and endometrial carcinoma (7.8, 55/708). Tumors with the highest absolute number of HBB-Mt tumors were NSCLC (7.0, 230/3307), CRC (8.1, 176/2161) and BC (6.7, 131/1960). In CRC, there was no significant difference in the prevalence of right-sided tumors between HBB-Wt v Mt (42% v 51, p = .06), nor in the prevalence of HBB-Mt by consensus molecular subtype ( p = .34). No significant enrichment of HBB-Mt across BC subtypes was observed (HR- HER2-: 7.8%, HR-HER2+: 9.7, HR+/HER2-:5.8, HR+/HER2+: 8.1, p = .34). No difference in the prevalence of pathogenic alterations was observed between HBB-Mt vs -Wt across NSCLC, CRC, and BC ( p > .05). HBB-Mt NSCLC were significantly enriched (GSEA) for genes related interferon /, inflammatory response and IL6/JAK/STAT3. No significant difference in OS was observed in CRC (median survival HBB-Wt: 957 days v -Mt: 1034, p = .43), NSCLC (-Wt: 591 v -Mt: 648, p = .59) or BC (-Wt: 924 v -Mt: 922, p = .61). Conclusions: No significant differences in the genomic landscape nor in OS of HBB-Mt vs HBB-Wt NSCLC, CRC or BC were observed. NSCLC HBB-Mt was enriched with inflammatory response genes. Future work should focus on potential role HBB-Mt plays in NSCLC.

A New Formula Based on Simple Blood Indices to Differentiate Beta Thalassemia Trait from Iron Deficiency Anemia.

Thalassemia is an inherited blood disorder with a defect in the sufficient production of a protein called hemoglobin. We aimed to investigate the simple blood indices of patients with Beta Thalassemia Trait (BTT) and Iron Deficiency Anemia (IDA) to propose a new formula using logistic regression for differentiate two characteristics from each other. Among the 702 records of the BTT Counseling Center (Khoy, Iran-2022), 292 cases (219 iron deficiency anemia (IDA) and 73 BTT) were eligible for the study. Blood indices such as RBC, HGB, HbA2 described and used to diagnose two types of participants. Blood indices had high multicollinearity that was modified. Logistic regression for blood indices fitted and goodness of fit indices with Area Under ROC curve (AUC) estimated. The average age of the participants was 24.56 yr. The status of Multicollinearity between independent variables was modified. The HGB, MCV, HbA2, and HbA variables were used in the model and only HbA2 status was significant (P<0.001). According to the output of the model, for each unit increase in HbA2, the chance of having BTT was about 8.5 times higher than IDA. The sensitivity, specificity, AUC curve, and accuracy of the final model were estimated to be 97, 72, 84, and 93%, respectively. A regression formula to differentiate BTT from IDA proposed. In studies related to the differentiation of the BTT from IDA, the presence of the HbA2 index in the model and prediction is very necessary.

Update on the practice of premarital screening for sickle cell traits in Africa: a systematic review and meta-analysis

BackgroundScreening for sickle cell traits before marriage or producing children is one of the outstanding preventive measures for sickle cell disease (SCD).The disease is a collection of inherited blood disorders that impact millions globally, with a predominant 75% occurrence in the sub-Saharan region. With increasing burden of SCD on the continent amidst a cost effective prevention method, no study has systematically reviewed or presented meta-analytic uptake or practice of premarital sickle cell trait screening.MethodsThis review systematically explored the uptake or practice of premarital genotype screening in Africa. We searched PubMed and Scopus databases for African studies on premarital screening for sickle cell traits.ResultsOur results indicate that the pooled uptake of premarital sickle cell trait screening in Africa is 47.82% (95% CI: [46.53–49.11]; I2: 98.95% [98.74–99.13]). Our review observed, a significant relationship between the awareness of sickle cell disease and the uptake of genotype screening; F(1, 13) = 12.04, p = 0.004). The model explained approximately 48.08% of the variation in genotype screening (R² = 0.4808) and predicted a 0.729 increase in the likelihood of genotype screening uptake for every unit rise in sickle cell disease awareness (β = 0.729, p = 0.004). Additionally, Pearson correlation (r = 0.6934) indicated a moderately strong positive correlation between the two variables.ConclusionWith over 75% of the global burden of sickle cell disease domiciled in Africa, the continent cannot overlook the cost of hemoglobinopathies. The uptake of sickle cell traits screening is suboptimal across the continent. To achieve the mandate of sustainable development goal number (3); to end preventable deaths of newborns and children under 5 years of age by 2030, there is need to intensify campaigns on premarital genetic screening through education and other health promotion tools.

Management of compound odontoma associated with unerupted maxillary permanent incisors: A case report

Introduction: Odontomas, the most common odontogenic tumors, result from developmental abnormalities where epithelial and mesenchymal cells grow, forming functional ameloblasts and odontoblasts. Typically asymptomatic, they are often associated with unerupted or impacted teeth. Odontomas are categorized as complex or compound, based on their tissue composition and structure. The preferred treatment is conservative surgical excision, followed by histopathological analysis for confirmation. Case History: A 13-year-old female patient came to the Pedodontic Clinic at RSGM Airlangga University with the chief complaint of unerupted upper front teeth. Intraoral eximination revealed no facial asymmetry. Intraoral examination revealed the absence of maxillary right central and lateral incisors with an asymptomatic swelling and no inflammation of the overlying mucosa. The patient had no history of systemic diseases such as heart disease or blood disorders, and there were no known allergies to food or medications. Discussion: Odontomas are generally asymptomatic and associated with unerupted or impacted teeth or retention of primary teeth. Removal of obstructions like odontome results in a spontaneous eruption of the impacted tooth. Another method currently being undertaken involves surgically exposing unerupted teeth and placing bonded attachment along with ligatures/e-chains for orthodontic traction so that it will speedup eruption process. Conclusion: The odontoma must be removed so that it will not disrupt dental growth and development, especially tooth eruption.

Frenectomy management for Ankyloglossia in a 1-Year-old patient under general anesthesia: A case report

Introduction: Ankyloglossia is defined as a congenital disorder that alters tongue mobility and function. It is listed as one of the possible reasons behind breastfeeding issues. The WHO currently recommends mothers to breastfeed exclusively up to 6 months of age, emphasizing the importance of promptly identifying any breastfeeding obstacles and determining the root cause of the problems as the primary focus. The purpose of writing this article is to describe a frenectomy as a surgical procedure that addresses ankyloglossia by excising the lingual frenulum with general anesthesia. Case History: A 1-year-old male patient presented at Dr. Saiful Anwar Regional General Hospital with complaints of difficulty in breastfeeding and consuming complementary foods, as well as prolonged pain experienced by the mother during breastfeeding. The patient had no history of systemic diseases such as heart disease or blood disorders, and there were no known allergies to food or medications. The patient was uncooperative (Frankl scale number 1). After analyzing the ankyloglossia, the choice of frenectomy with general anesthesia was chosen to treat this case. Discussion: Dental examinations and treatments for uncooperative 1-year-old children can be challenging in regular dental offices. Effective behavioral management, such as general anesthesia (GA), is required for safe and efficient treatment. GA involves a multidisciplinary team to oversee the procedure stages, allowing for one-visit treatment, reduced anxiety, and a safer, less painful dental experience. Conclusion: Frenectomy procedure under GA has been performed as an option to facilitate restorative therapy, improve nutritional intake, and quality of life.

Blood and bone marrow cell disorders in the stages of progressive diabetes in mice

Blood and bone marrow cell disorders in the stages of progressive diabetes in mice

Xuezheng Quanji, the earliest monograph on blood disorder

Xuezheng Quanji(«») written by Sun Guangyu, a doctor in the Ming Dynasty, is the first known book on blood disorders in China. The book mainly deals with bleeding. The book begins with a collection of the Neijing and the treatises of the sages, focusing on systematically summarizing the theories and experiences of the past dynasties in the treatment of bleeding, interspersed with Sun's own opinions.The main part discusses four types of bleeding, summarizing Sun's profound experience in clinical practice, and many of his personal creative opinions.In terms of causes,Sun believed that there are three causes of bleeding and more due to heat. In terms of treatment,he opposed the abuse of bitter cold and attached great importance to nourishing yin and strengthening kidney and proposed four treatment methods of dispelling stasis, nourishing Yin and suppressing Yang, regulating Qi and blood, and tonifying deficiency. He advocated that bleeding should not be treated quickly, and emphasized that the disease should be judged according to the bleeding location and bleeding color to use herbs flexibly.Special attention should be paid to daily life care during and after illness as well.

Enhancing prime editing in hematopoietic stem and progenitor cells by modulating nucleotide metabolism.

Therapeutic prime editing of hematopoietic stem and progenitor cells (HSPCs) holds great potential to remedy blood disorders. Quiescent cells have low nucleotide levels and resist retroviral infection, and it is possible that nucleotide metabolism could limit reverse transcription-mediated prime editing in HSPCs. We demonstrate that deoxynucleoside supplementation and Vpx-mediated degradation of SAMHD1 improve prime editing efficiency in HSPCs, especially when coupled with editing approaches that evade mismatch repair.

#1222 Crovalimab: patient preferences and ongoing phase III COMMUTE trials in acute haemolytic uraemic syndrome (aHUS)

Abstract Background and Aims aHUS is a rare, life-threatening, complement-mediated disease characterised by thrombotic microangiopathies (TMAs). Existing C5 inhibitor (C5i) therapies, such as eculizumab (ecu) and ravulizumab (ravu), are effective for aHUS management but can be burdensome in both adults and children, typically requiring regular intravenous (IV) infusions every 2 weeks (Q2W, ecu) or every 8 weeks (ravu). Crovalimab (crova), a novel C5i with low-volume, subcutaneous (SC) administration every 4 weeks (Q4W), allows for convenient self-administration outside of a healthcare setting. Crova is currently being evaluated in two ongoing global, Phase III, single-arm trials in aHUS: COMMUTE-a (NCT04861259) and COMMUTE-p (NCT04958265). The efficacy and safety of crova have also been evaluated in patients (pts) with paroxysmal nocturnal haemoglobinuria (PNH), another complement-mediated rare blood disorder, in the global, randomised, Phase III COMMODORE 1 (NCT04432584) and COMMODORE 2 (NCT04434092) trials (Röth EHA 2023; #S181, Scheinberg EHA 2023; #S183). Here, we report pt preference data from COMMODORE 1 and 2. Method COMMODORE 1 and 2 enrolled C5i-experienced and C5i-naive pts with PNH, respectively. Pts were randomised 1:1 in COMMODORE 1 and 2:1 in COMMODORE 2 to receive crova (weight-based tiered dosing regimen consisting of loading doses followed by SC Q4W maintenance) or ecu (900 mg IV Q2W) over a 24-week primary treatment period. After completing 24 weeks of treatment, all pts received crova if continuing the trial. Treatment preference was assessed in adult pts using the validated Patient Preference Questionnaire (PPQ) after 17 weeks of crova treatment in C5i-experienced pts randomised to crova in COMMODORE 1 and in pts initially randomised to ecu who switched to crova at Week 25 in both COMMODORE 1 and 2. COMMUTE-a is enrolling pts with aHUS aged ≥12 years and weighing ≥40 kg (N ≈ 80), while COMMUTE-p is enrolling pts with aHUS aged ≥28 days to &amp;lt;18 years and weighing ≥5 kg (N ≈ 45). Both studies are enrolling 3 cohorts (Fig. 1): (1) Naive: pts not previously treated with a C5i (n ≈ 40 in COMMUTE-a; n ≈ 20 in COMMUTE-p), (2) Switch: pts switching from ecu or ravu (n≈40 in COMMUTE-a; n ≥ 20 in COMMUTE-p), (3) C5 polymorphism cohort in COMMUTE-a: pts with known C5 polymorphisms (n ≤ 5); pretreated cohort in COMMUTE-p: pts previously treated with and discontinued ecu or ravu (n ≤ 10). In both COMMUTE studies, pts will receive weight-based tiered crova dosing consisting of loading doses (IV and SC) followed by SC Q4W maintenance (or Q2W if &amp;lt;20 kg) from Week 5 onward. The primary efficacy objective of both studies is to assess the proportion of C5i-naive pts with complete TMA response from baseline to Week 25. Secondary efficacy endpoints include change from baseline in dialysis requirement status and estimated glomerular filtration rate. Safety, pharmacokinetics, immunogenicity, biomarkers, and pt-reported fatigue will also be assessed. Treatment preference will be assessed using the PPQ in pts ≥12 years old and in caregivers of children &amp;lt;12 years old. Results 89 pts were randomised in COMMODORE 1 (crova: n = 45; ecu: n = 44) and 204 in COMMODORE 2 (crova: n = 135; ecu: n = 69). Of pts randomised to crova in COMMODORE 1, 33 (85%) of 39 pts assessed at Week 17 preferred crova over ecu. Of pts randomised to ecu who switched to crova after the primary treatment period, 27 (96%) of 28 pts who answered the questionnaire in COMMODORE 1 and 32 (84%) of 38 in COMMODORE 2 preferred crova (Fig. 2). The top reasons selected for crova preference over ecu were that the treatment required fewer hospital visits, was easier to administer, took less time to administer, and provided better quality of life (Kulasekararaj ASH 2023; #5628). COMMUTE-a and COMMUTE-p are currently open for recruitment in 17 and 14 countries, respectively. Conclusion Crova was preferred to ecu by most C5i-naive and switch pts with PNH in COMMODORE 1 and 2, largely due to faster, easier administration. Crova, with SC Q4W (or Q2W in pts &amp;lt;20 kg with aHUS) self-administration, can potentially reduce treatment burden vs currently approved C5 is in aHUS. The COMMUTE-a and COMMUTE-p trials evaluating crova in aHUS are currently enrolling.

The effect of bone marrow mesenchymal stromal cell exosomes on acute myeloid leukemia’s biological functions: a focus on the potential role of LncRNAs

Acute myeloid leukemia represents a group of malignant blood disorders that originate from clonal over-proliferation and the differentiation failure of hematopoietic precursors, resulting in the accumulation of blasts in the bone marrow. Mesenchymal stromal cells (MSCs) have been shown to exert diverse effects on tumor cells through direct and indirect interaction. Exosomes, as one of the means of indirect intercellular communication, are released from different types of cells, including MSCs, and their various contents, such as lncRNAs, enable them to exert significant impacts on target cells. Our study aims to investigate the effects of BM-MSC exosomes on the cellular and molecular characterization of HL-60 AML cells, particularly detecting the alterations in the expression of lncRNAs involved in AML leukemogenesis, cell growth, drug resistance, and poor prognosis. BM-MSCs were cultured with serum-free culture media to isolate exosomes from their supernatants. The validation of exosomes was performed in three stages: morphological analysis using TEM, size evaluation using DLS, and CD marker identification using flow cytometry. Subsequently, the HL-60 AML cells were treated with isolated BM-MSC exosomes to determine the impact of their contents on leukemic cells. Cell metabolic activity was evaluated by the MTT assay, while cell cycle progression, apoptosis, ROS levels, and proliferation were assessed by flow cytometry. Furthermore, RT-qPCR was conducted to determine the expression levels of lncRNAs and apoptosis-, ROS-, and cell cycle-related genes. MTT assay and flow cytometry analysis revealed that BM-MSC exosomes considerably suppressed cell metabolic activity, proliferation, and cell cycle progression. Also, these exosomes could effectively increase apoptosis and ROS levels in HL-60 cells. The expression levels of p53, p21, BAX, and FOXO4 were increased, while the BCL2 and c-Myc levels decreased. MALAT1, HOTAIR, and H19 expression levels were also significantly decreased in treated HL-60 cells compared to their untreated counterparts. BM-MSC exosomes suppress cell cycle progression, proliferation, and metabolic activity while simultaneously elevating the ROS index and apoptosis ratio in HL-60 cells, likely by reducing the expression levels of MALAT1, HOTAIR, and H19. These findings suggest that BM-MSC exosomes might serve as potential supportive therapies for leukemia.

Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial.

To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer. This is a randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients had advanced incurable cancer and fatigue >3/10. Principal exclusions were hypertension; psychiatric, cardiovascular, cerebrovascular, renal, liver, or blood disorders; substance dependency; and epilepsy. Patients were randomly assigned 1:1 methylphenidate or placebo starting at 5 mg twice daily. Dose of methylphenidate/placebo was titrated once per week, over 6 weeks, up to a maximum of 20 mg three times daily. Trial ended at 10 weeks. Primary outcome was the difference in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores between groups at 6 ± 2 weeks. Secondary outcomes included adverse effects, quality of life, and mood. One hundred sixty-two patients (73 men; mean, 65.8; standard deviation [SD], 10.3 years) were randomly assigned, and three were excluded from analysis. Seventy-seven were allocated placebo (baseline FACIT-F = 22 [SD, 10]); 82 were allocated methylphenidate (FACIT-F = 20 [SD, 9]). After 6 ± 2 weeks, FACIT-F scores were 1.97 points (95% CI, -0.95 to 4.90; P = .186) higher (better) on methylphenidate than placebo. Across 10 weeks of the study, FACIT-F was nominally higher in the methylphenidate group versus placebo (Diff, 2.20 [95% CI, 0.39 to 4.01]), but this did not reach the minimally clinically important difference (5-points). At 6 weeks, there were no differences between groups in quality-of-life or symptom domains except for depression scores (nominally reduced in the methylphenidate group: Diff, -1.35 [95% CI, -2.41 to -0.30]). There were no differences in mortality or serious adverse events. After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well-tolerated.

Current and Future Therapeutics for Treating Patients with Sickle Cell Disease.

Sickle cell disease (SCD) is the most common genetic blood disorder in the United States, with over 100,000 people suffering from this debilitating disease. SCD is caused by abnormal hemoglobin (Hb) variants that interfere with normal red blood cell (RBC) function. Research on SCD has led to the development and approval of several new SCD therapies in recent years. The recent FDA-approved novel gene therapies are potentially curative, giving patients an additional option besides a hematopoietic bone marrow transplant. Despite the promise of existing therapies, questions remain regarding their long-term pharmacological effects on adults and children. These questions, along with the exorbitant cost of the new gene therapies, justify additional research into more effective therapeutic options. Continual research in this field focuses on not only developing cheaper, more effective cures/treatments but also investigating the physiological effects of the current therapies on SCD patients, particularly on the brain and kidneys. In this article, we undertake a comprehensive review of ongoing clinical trials with completion dates in 2024 or later. Our exploration provides insights into the landscape of current therapeutics and emerging novel therapies designed to combat and potentially eradicate SCD, including the latest FDA-approved gene therapies.

Lipid and hemolysis parameters predicting acute chest syndrome in adulthood with sickle cell disease

Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 people in the United States and is one of the most common monogenic diseases. A serious complication of SCD is acute chest syndrome (ACS). ACS is a condition with a high rate of morbidity and mortality. The aim of the study was to assess hemolysis and lipid parameters in a cohort of confirmed SCD patients to predict ACS development in the following year.Standard lipid were performed (triglycerides, total cholesterol, high-density cholesterol, low-density cholesterol) panel to calculate of non-HDL-C, large buoyant LDL cholesterol (lbLDL-C) and small dense LDL cholesterol (sdLDL-C) with Sampson equation. Hemolysis and hematologic parameters were also evaluated.Among 91 patients included between September 2018 and June 2021, thirty-seven patients had history of ACS and 6 patients developed ACS during following year. In unadjusted logistic regression, total bilirubin was associated with ACS occurrence (RR: 1.2 [1.05–1.51] p = 0.013). Concerning lipid profile, non-HDL-C (RR: 0.87 [0.0.67–0.99] p = 0.04) and sdLDL-C (RR: 0.78 [0.49–0.96] p = 0.03) were associated with ACS occurrence decrease. C-reactive protein was associated with ACS occurrence (RR: 1.27 [1.065–1.85] p = 0.011).Based on these findings, this study demonstrated that several biomarker easily available can be used at steady state to predict ACS in the following year. The validation of these results are required to ensure the reproducibility of the findings.